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Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor r Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

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Author(s)
Kwi-Hyun BaeJung Beom SeoHye-Young SeoSun Hee KangHui-Jeon JeonJae Man LeeSungwoo LeeJung-Guk KimIn-Kyu LeeGwon-Soo JungKeun-Gyu ParkYun-A Jung
Keimyung Author(s)
Kang, Sun Hee
Department
Dept. of Internal Medicine (내과학)
Journal Title
Endocrinology and Metabolism
Issued Date
2017
Volume
32
Issue
1
Keyword
Renal tubulointerstitial fibrosisLobeglitazoneTransforming growth factor betaUnilateral ureteral obstruction
Abstract
Background: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease.
Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy,
much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone,
a novel PPARγ agonist, on renal fibrosis in mice.
Methods: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced
renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in
renal tubulointerstitial fibrosis through in vivo and in vitro study.
Results: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal
atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction
and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation,
α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial
cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by
inhibition of the TGF-β/Smad signaling pathway.
Conclusion: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting
that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
Keimyung Author(s)(Kor)
강선희
Publisher
School of Medicine
Citation
Kwi-Hyun Bae et al. (2017). Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor r Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice. Endocrinology and Metabolism, 32(1), 115–123. doi: 10.3803/EnM.2017.32.1.115
Type
Article
ISSN
2093-596X
DOI
10.3803/EnM.2017.32.1.115
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32399
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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